The analysis of circulating tumor DNA (ctDNA), minute quantities of cell free DNA of tumor origin within the blood of cancer patients, provides a non-invasive window into a patient's disease state. While modern analytical tools have provided glimpses into the utility of ctDNA to guide patient care, their clinical adaptation has been limited by technical barriers. Currently all technologies for analyzing ctDNA are too costly inapplicable to the majority of patients, or extremely time consuming. Proposed here is a radically new testing platform called iWISE (Isoentropic Wildtype Suppressive Enrichment) that enables the accurate quantification and genotyping of ctDNA within the majority of cancer patients at minimal cost, incredible speed and without the need for proprietary equipment. iWISE is based on a novel biochemical concept called isoentropic strand-displacement network. The iWISE technology will be further developed into two commercial kits: one for quantification of known or suspected mutations in cell-free DNA using a simple qPCR setup; and the other for discovery of unknown mutations in cell-free DNA using a multiplexed, PCR-based mutation-enrichment reaction.